Loss of spatial learning in a patient with topographical disorientation in new environments

The case is described of a patient who, following cerebral hypoxia, developed severe difficulty in orienting himself in new environments in the context of a mild global amnesic syndrome. Some episodes he related suggested that his main difficulty was remembering the spatial/directional value of landmarks he recognised. A neuroradiological examination documented severe bilateral atrophy of the hippocampi associated with atrophic changes in the cerebral hemispheres, most marked in the dorsal regions. Neuropsychological and experimental evaluation showed a severe deficit of spatial learning with substantially preserved ability to learn verbal and visual-object information. He was also virtuall…

Lexical and conceptual components of stem completion priming in patients with Alzheimer's disease

This study evaluated the hypothesis of dissociation between normal lexical but deficient conceptual repetition priming in patients with Alzheimer's disease (AD). For this purpose, we administered to patients with AD and age-matched normal controls the Stem Completion task. In Experiment 1, the level of word processing during study was manipulated by requiring subjects to count vowels (graphemic condition) or generate meanings (semantic condition) of target words. In Experiment 2, the presentation modality was varied during the study to obtain an intramodal and crossmodal repetition priming. Probably due to a floor effect of performance in the graphemic condition, in Experiment 1, AD patient…

Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease

BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. METHODS: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits…

Resonance of cortico-cortical connections of the motor system with the observation of goal directed grasping movements

Goal directed movements require the activation of parietal, premotor and primary motor areas. In monkeys, neurons of these areas become active also during the observation of movements performed by others, especially for coding the goal of the action (mirror system). Using bifocal transcranial magnetic stimulation (TMS) in healthy subjects, we tested whether the observation of goal directed reach to grasp actions may lead to specific changes in the short-latency connections linking key areas of the mirror system, such as the anterior intraparietal cortex (AIP) and the ventral premotor cortex (PMv), with the primary motor cortex (M1). We found that AIP-M1 and PMv-M1 cortico-cortical interacti…

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

BACKGROUND: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-epsilon4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. OBJECTIVE: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. METHODS: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognit…

The influence of rTMS over prefrontal and motor areas in a morphological task: grammatical vs. semantic effects

We investigated the differential role of two frontal regions in the processing of grammatical and semantic knowledge. Given the documented specificity of the prefrontal cortex for the grammatical class of verbs, and of the primary motor cortex for the semantic class of action words, we sought to investigate whether the prefrontal cortex is also sensitive to semantic effects, and whether the motor cortex is also sensitive to grammatical class effects. We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefontal cortex (first experiment) and of the motor area (second experiment). In the first experiment we found that rTMS applied to t…

Recognition memory for single items and for associations in amnesic patients

Recognition memory performance reflects two distinct processes or types of memory referred to as recollection and familiarity. According to theoretical claims about the two types of memory, single item and associative recognition tasks can be used as an experimental method to distinguish recollection and familiarity processes. Associative recognition decisions can be used as an index of recollection while memory for single items is mostly based on familiarity judgement. We employed this procedure to examine a possible dissociation in the memory performance of amnesic patients between spared single item and impaired associative recognition. Twelve amnesic patients, six with damage confined t…

The Neural Correlates of Grammatical Gender: An fMRI Investigation

Abstract In an fMRI experiment, subjects saw a written noun and made three distinct decisions in separate sessions: Is its grammatical gender masculine or feminine (grammatical feature task)? Is it an animal or an artifact (semantic task)? Does it contain a /tch/ or a /k/ sound (phonological task)? Relative to the other experimental conditions, the grammatical feature task activated areas of the left middle and inferior frontal gyrus and of the left middle and inferior temporal gyrus. These activations fit in well with neuropsychological studies that document the correlation between left frontal lesions and damage to morphological processes in agrammatism, and the correlation between left t…

Cortical networks of procedural learning: Evidence from cerebellar damage

The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitiv…

rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory.

The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral …

Selective sparing of face learning in a global amnesic patient

Objective - To test the hypothesis that visual memory for faces can be dissociated from visual memory for topographical material. Method - A patient who developed a global amnesic syndrome after acute carbon monoxide poisoning is described. A neuroradiological examination documented severe bilateral atrophy of the hippocampi. Results - Despite a severe anterograde memory disorder involving verbal information, abstract figures, concrete objects, topographical scenes, and spatial information, the patient was still able to learn previously unknown human faces at a normal (and, in some cases, at a higher) rate. Conclusions - Together with previous neuropsychological evidence documenting selecti…

Spatial-temporal interactions in the human brain

The review summarises current evidence on the cognitive mechanisms for the integration of spatial and temporal representations and of common brain structures to process the where and when of stimuli. Psychophysical experiments document the presence of spatially localised distortions of sub-second time intervals and suggest that visual events are timed by neural mechanisms that are spatially selective. On the other hand, experiments with supra-second intervals suggest that time could be represented on a mental time-line ordered from left-to-right, similar to what is reported for other ordered quantities, such as numbers. Neuroimaging and neuropsychological findings point towards the posterio…

Recognition memory and prefrontal cortex: Dissociating recollection and familiarity processes using rTMS

Recognition memory can be supported by both the assessment of the familiarity of an item and by the recollection of the context in which an item was encountered. The neural substrates of these memory processes are controversial. To address these issues we applied repetitive transcranial magnetic stimulation (rTMS) over the right and left dorsolateral prefrontal cortex (DLPFC) of healthy subjects performing a remember/know task. rTMS disrupted familiarity judgments when applied before encoding of stimuli over both right and left DLPFC. rTMS disrupted recollection when applied before encoding of stimuli over the right DLPFC. These findings suggest that the DLPFC plays a critical role in recog…

Modulation of excitatory and inhibitory circuits for visual awareness in the human right parietal cortex.

The balance of specific patterns of excitation and inhibition in critical regions of both hemispheres could be relevant in orienting attention over the extrapersonal space. In the present study a group of normal subjects had to detect small rectangular stimuli presented briefly on a computer screen in three different conditions: unilateral presentation either to left or right visual periphery or bilateral simultaneous presentation. Paired transcranial magnetic stimulation (TMS), was applied over the right parietal cortex 150 ms after the presentation of the visual stimuli with different inter-stimulus intervals (ISIs: 1, 3,5 and 10 ms). When paired TMS was applied 150 ms, but not 100 ms, af…

Recollection and familiarity in hippocampal amnesia

Currently, there is a general agreement that two distinct cognitive operations, recollection and familiarity, contribute to performance on recognition memory tests. However, there is a controversy about whether recollection and familiarity reflect different memory processes, mediated by distinct neural substrates (dual-process models), or whether they are the expression of memory traces of different strength in the context of a unitary declarative memory system (unitary-strength models). Critical in this debate is the status of recognition memory in hippocampal amnesia and, in particular, whether the various structures in the medial temporal lobe (MTL) contribute differentially to the recol…

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respectiv…

The role of right and left posterior parietal cortex in the modulation of spatial attentional biases by self and non-self face stimuli

In the present research we investigated whether the direction of the attentional bias in line bisection judgment displayed by healthy subjects is influenced by the evaluation of the social distance between self and other. We used inhibitory repetitive transcranial magnetic stimulation (rTMS) trains over the right and left parietal cortex to investigate the role of these regions in the task. Following right parietal rTMS, the self face is perceived as closer when it is located at the right line endpoint; following left parietal rTMS, the self face is perceived as closer when it is located at the left line endpoint. In both cases, the side of space ipsilateral to the rTMS is underestimated fr…

Continuous theta burst stimulation (cTBS) on left cerebellar hemisphere affects mental rotation tasks during music listening.

Converging evidence suggests an association between spatial and music domains. A cerebellar role in music-related information processing as well as in spatial-temporal tasks has been documented. Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR) or abstract (AMR) mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS) of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a “Moz…

"I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in th…

rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease

The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.

Differential involvement of the left frontal and temporal regions in verb naming: A tDCS treatment study

Purpose: In aphasic patients, some studies have already emphasized the efficacy of transcranial direct current stim- ulation (tDCS) during the treatment of noun retrieval deficits. To date, in the same population, there are have been no studies addressing tDCS effects in the recovery of verb retrieval deficits. In this study, we wanted to test the potential of tDCS to improve verb production in a group of aphasic patients. Methods: Seven chronic subjects participated in an intensive language training for their difficulties in action naming. Each subject was treated with tDCS (20 min., 1 mA) over the left hemisphere in three different conditions: anodic tDCS over Wernicke's area, anodic tDCS…

Functional anatomy of motor recovery after early brain damage

Functional magnetic resonance imaging and transcranial magnetic stimulation were used to examine a 34 year-old right-handed patient, who, at the age of 6 years, had experienced sudden right hemiplegia, seizures, and stupor during a bout of measles encephalitis, followed by incomplete distal right motor recovery. Morphological MRI showed massive unilateral enlargement of the left ventricle, associated with extreme thinning of the white and gray matter, with partial preservation of the pyramidal tract. Functional MRI and transcranial magnetic stimulation revealed reorganization of the motor cortices, and integrity of the corticospinal pathway, respectively. Our findings indicate that complete…

Temporo-parietal junction is involved in attribution of hostile intentionality in social interactions: an rTMS study.

The temporal-parietal junction (TPJ) is a brain area implicated in social cognition, attention, integrating body-related information and self-processing. We investigated involvement of both the left and the right TPJ in a complex social cognitive task that required attributing intentions to other people. Fourteen healthy subjects participated in experiments that involved simulating interactions with other people in everyday conflicting situations. The task was performed following application of inhibitory trains of repetitive transcranial magnetic stimulation (rTMS) to the right and the left TPJ and to a control occipital brain site. Results showed a different pattern of involvement for the…

Cerebellar Contribution to Mental Rotation: a cTBS Study

A cerebellar role in spatial information processing has been advanced even in the absence of physical manipulation, as occurring in mental rotation. The present study was aimed at investigating the specific involvement of left and right cerebellar hemispheres in two tasks of mental rotation. We used continuous theta burst stimulation to downregulate cerebellar hemisphere excitability in healthy adult subjects performing two mental rotation tasks: an Embodied Mental Rotation (EMR) task, entailing an egocentric strategy, and an Abstract Mental Rotation (AMR) task entailing an allocentric strategy. Following downregulation of left cerebellar hemisphere, reaction times were slower in comparison…

Developmental dissociation between visual and auditory repetition priming: The role of input lexicons

Contrasting theories posit the source of verbal repetition priming in the activation of preexisting memory representations in the input lexicons or, alternatively, in the formation of new episodic memory traces. The two hypotheses predict different outcomes from the comparison of developmental rates of visual and auditory verbal repetition priming. The activation theory predicts a developmental dissociation between the early maturation of auditory priming and the later maturation of visuo-verbal priming, contingent upon the discrepant acquisition rates of the auditory and visual input lexicons. The episodic theory, instead, does not make such an assumption. We administered visual and audito…

The representation of segmental information: an fMRI investigation of the consonant-vowel distinction

Harvard University, Cambridge, MA, USAAvailable online 23 July 2004IntroductionRecent studies suggest that consonants and vowels are repre-sented separately in cognitive/neural space. Much of the evidencecomes from research on dysgraphia (for review, see Miceli & Cap-asso, submitted). In the first place, letter substitution errors preservethe consonant/vowel (CV) status of the target (e.g., cinema fi ciremaor cinoma, but not cintma). Second, there are reports of selectiveimpairment for consonants or vowels. Additional evidence comesfrom disorders of phonology, demonstrating the dissociability be-tween consonants and vowels (Caramazza, Chialant, Capasso, Mthe ISI was variable (mean 6.75 s). Th…

Optokinetic stimulation affects temporal estimation in healthy humans

The representation of time and space are closely linked in the cognitive system. Optokinetic stimulation modulates spatial attention in healthy subjects and patients with spatial neglect. In order to evaluate whether optokinetic stimulation could influence time perception, a group of healthy subjects performed "time-comparison" tasks of sub- and supra-second intervals before and after leftward or rightward optokinetic stimulation. Subjective time perception was biased by the direction of optokinetic stimulation. Rightward optokinetic stimulation induced an overestimation of time perception compared with baseline and leftward optokinetic stimulation. These results indicate a directional bias…

Keeping memory for intentions: A cTBS investigation of the frontopolar cortex

The present study aimed to investigate the role of frontopolar cortex in prospective memory (PM) by means of inhibitory theta-burst stimulation (cTBS). "Experiment 1"-8 volunteers were evaluated after inhibitory cTBS over left Brodmann area (BA) 10, right BA10, and Cz. In the PM procedure, sequences of 4 words each were presented. During the intersequence delay, subjects had to repeat the sequence in the observed order (ongoing task forward) or in the reverse order (backward). At the occurrence of a target word, subjects had to press a key on the keyboard (PM task). Recall and recognition of the target words were also tested. PM accuracy was lower after cTBS over left BA10 compared with Cz …

Neural networks engaged in milliseconds and seconds time processing: evidence from transcranial magnetic stimulation and patients with cortical or subcortical dysfunction

Here, we review recent transcranial magnetic stimulation studies and investigations in patients with neurological disease such as Parkinson's disease and stroke, showing that the neural processing of time requires the activity of wide range-distributed brain networks. The neural activity of the cerebellum seems most crucial when subjects are required to quickly estimate the passage of brief intervals, and when time is computed in relation to precise salient events. Conversely, the circuits involving the striatum and the substantia nigra projecting to the prefrontal cortex (PFC) are mostly implicated in supra-second time intervals and when time is processed in conjunction with other cognitiv…

Specific forms of neural activity associated with tactile space awareness

Left tactile extinction, in which a left tactile stimulus fails to access consciousness only when a right stimulus is presented simultaneously, offers a model for studying tactile awareness from its transitory absence. Pairs of transcranial magnetic stimuli (TMS) on the parietal cortex inhibit contralateral tactile perception when separated by an interval of 1 ms. We have applied this technique on the left parietal cortex of right brain damaged (RBD) patients and normal subjects and have shown a selective lack of paired TMS inhibitory effects on right tactile perception of patients during bimanual stimulation. TMS effects were normal during unimanual right stimulation. These results suggest…

Prefrontal and temporo-parietal involvement in taking others' perspective: TMS evidence.

INTRODUCTION: Understanding the mental states of others entails a number of cognitive processes known as Theory of Mind (ToM). Behavioural and functional neuroimaging evidence suggests that prefrontal and temporo-parietal cortices are involved in these abilities. The present study was aimed at investigating the role of the dorsolateral prefrontal cortex and temporo-parietal junction in ToM by using a repetitive transcranial magnetic stimulation (rTMS) paradigm. MATERIAL AND METHODS: Eleven healthy subjects participated in the study. The experimental ToM procedure was constituted by false belief and faux-pas written stories. Subjects were evaluated in baseline condition (Sham) and after 1Hz …

Changes in intracortical circuits of the human motor cortex following theta burst stimulation of the lateral cerebellum

Objective: The cerebellum takes part in several motor functions through its influence on the motor cortex (M1). Here, we applied the theta burst stimulation (TBS) protocol, a novel form of repetitive Transcranial Magnetic Stimulation (rTMS) over the lateral cerebellum. The aim of this study was to test whether TBS of the lateral cerebellum could be able to modulate the excitability of the contralateral M1 in healthy subjects. Methods: Motor-evoked potentials (MEPs) amplitude, short intracortical inhibition (SICI), long intracortical inhibition (LICI) and short intracortical facilitation (SICF) were tested in the M1 before and after cerebellar continuous TBS (cTBS) or intermittent TBS (iTBS)…

Selective proper name anomia in a patient with asymmetric cortical degeneration

All cases of selective anomic deficit for proper names described until now are a consequence of focal cerebral lesions. In the present paper, we report the case of a patient, AF, with a deficient access to proper names of persons and normal access to common names probably subsumed by a degenerative process of the left cerebral hemisphere. MRI evidenced an atrophy of the left temporal lobe and SPECT highlighted hypoperfusion of the left hemisphere. Neuropsychological examination documented a deficient production of proper names belonging to famous personalities both on visual presentation and verbal definition. Moreover, on verbal fluency tasks, AF was poor for the categories of famous peopl…

Suppression of extinction with TMS in humans: from healthy controls to patients.

We review a series of studies exemplifying some applications of single-pulse and paired-transcranial magnetic stimulation (TMS) in the study of spatial attention and of its deficits. We will focus primarily on sensory extinction, the failure to consciously perceive a contralesional sensory stimulus only during bilateral stimulation of homologous surfaces. TMS studies in healthy controls show that it is possible either to interfere or modulate the excitability of the parietal cortex during sensory (i.e. tactile and visual) attentional tasks, thus reproducing a condition of virtual extinction. TMS studies in patients with unilateral (mainly right) brain damage show that the modulation of the …

High-frequency rTMS improves time perception in Parkinson disease.

Patients with Parkinson disease (PD) are impaired in time processing. The authors investigated the effects of high-frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with PD performing a time reproduction task. The authors found significant improvement in time processing induced by rTMS when trains were applied over the right dorsolateral prefrontal cortex (DLPFC) but not over the supplementary motor area, suggesting that the circuit involving the basal ganglia and the DLPFC might constitute the neural network subserving time perception.

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016

Objective This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy w…

Perceiving numbers alters time perception.

The representation of time, space and numbers are strictly linked in the primate's cognitive system. Here we show that merely looking at number symbols biases a temporal judgment on their duration depending upon the number's magnitude. In a first experiment, a group of healthy subjects was submitted to a time estimation task, requiring to judge whether the duration of a test stimulus was longer or shorter than that of a previous reference fixed stimulus (digit 5; duration 300 ms). Test stimuli were the digits 1, 5 and 9 ranging between 250 and 350 ms. The main results showed that temporal perception was biased according to the magnitude expressed by the digit: low digits (i.e. 1) leading to…

P 61. Is high frequency rTMS a new tool in remediating dyslexia?

Introduction Evidence from functional neuroimaging has reported hypoactivation of the left parieto-temporal regions in children and adults with dyslexia when they engage in reading-related tasks (Shaywitz et al., 2002; Richlan et al., 2011). Studies on the remediation of dyslexia have consistently found that remedial treatment improves reading ability and increases activation in critical brain areas (Temple et al., 2003; Hoeft et al., 2011). Objectives We wanted to determine whether high frequency repetitive trancranial magnetic stimulation (hf-rTMS) over areas that are underactive in dyslexics during reading, such as the left superior temporal gyrus (STG) and the left inferior parietal lob…

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

How to improve reading skills in dyslexics: the effect of high frequency rTMS.

The latest progress in understanding remediation of dyslexia underlines how some changes in brain are a necessary mechanism of improvement. We wanted to determine whether high frequency repetitive transcranial magnetic stimulation (hf-rTMS) over areas that are underactive during reading in dyslexics, would improve reading of dyslexic adults. We applied 5Hz-TMS over both left and right inferior parietal lobule (IPL) and superior temporal gyrus (STG) prior to word, non-word and text reading aloud. Results show that hf-rTMS stimulation over the left IPL improves non-word reading accuracy and hf-rTMS stimulation over the left STG increases word reading speed and text reading accuracy. Moreover …

Processing Past Tense in the left cerebellum

We report the case of a patient with ischemic lesion of the left cerebellum, who showed specific deficits in processing past versus future tense of action verbs. These findings confirm, in the presence of cerebellar damage, previous results obtained with transcranial magnetic stimulation in healthy subjects and suggest a specificity of the left cerebellum for preparation of responses to the past tense of action verbs. As part of the procedural brain, the cerebellum could play a role in applying the linguistic rules for selection of morphemes typical of past and future tense formation.

The use of transcranial magnetic stimulation in spatial cognition

In vivo definition of parieto-motor connections involved in planning of grasping movements

We combined bifocal transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) tractography to investigate in humans the contribution of connections originating from different parietal areas in planning of different reaching to grasp movements. TMS experiments revealed that in the left hemisphere functional connectivity between the primary motor cortex (M1) and a portion of the angular gyrus (AG) close to the caudal intraparietal sulcus was activated during early preparation of reaching and grasping movements only when the movement was made with a whole hand grasp (WHG) towards objects in contralateral space. In contrast, a different pathway, linking M1 with a part of the su…

Repetitive TMS of cerebellum interferes with millisecond time processing

Time processing is important in several cognitive and motor functions, but it is still unclear how the human brain perceives time intervals of different durations. Processing of time in millisecond and second intervals may depend on different neural networks and there is now considerable evidence to suggest that these intervals are possibly measured by independent brain mechanisms. Using repetitive transcranial magnetic stimulation (rTMS), we determined that the cerebellum is essential in explicit temporal processing of millisecond time intervals. In the first experiment, subjects' performance in a time reproduction task of short (400-600 ms) and long (1,600-2,400 ms) intervals, were evalua…

The Right Frontopolar Cortex Is Involved in Visual-Spatial Prospective Memory

The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory t…

Changes in Cerebello-motor Connectivity during Procedural Learning by Actual Execution and Observation

Abstract The cerebellum is involved in motor learning of new procedures both during actual execution of a motor task and during observational training. These processes are thought to depend on the activity of a neural network that involves the lateral cerebellum and primary motor cortex (M1). In this study, we used a twin-coil TMS technique to investigate whether execution and observation of a visuomotor procedural learning task is related to modulation of cerebello-motor connectivity. We observed that, at rest, a magnetic conditioning pulse applied over the lateral cerebellum reduced the motor-evoked potentials obtained by stimulating the contralateral M1, indicating activation of a cerebe…

Integration of cognitive allocentric information in visuospatial short-term memory through the hippocampus

Visuospatial short-term memory relies on a widely distributed neocortical network: some areas support the encoding process of the visually acquired spatial information, whereas other ares are more involved in the active maintenance of the encoded information. Recently, in a pointing to remembered targets task, it has been shown in healthy subjects that, for memory delays of 5 s, spatial errors are affected also by cognitive allocentric information, i.e., covert spatial information derived from a pure mental representation. We tested the effect of a lesion of the hippocampus on the accuracy of pointing movements toward remembered targets, with memory delays falling in the 0.5-30 s range. The…

Representation of time intervals in the right posterior parietal cortex: implications for a mental time line

Space and time interact with each other in the cognitive system. Recent studies indicate the posterior parietal cortex (PPC) as the neural correlate of spatial-temporal interactions. We studied whether the contribution of the PPC becomes critical in tasks requiring the performance of spatial computations on time intervals. We adopted an integrated neuropsychological and transcranial magnetic stimulation (rTMS) approach, presenting behavioural timing tasks to both healthy subjects and right-brain-damaged patients with and without evidence of spatial neglect. rTMS of the right PPC of healthy subjects induced a lateralised bias during a task requiring setting the midpoint of a time interval. T…

Memory for time intervals is impaired in left hemi-Parkinson patients.

The basal ganglia have been proposed as one of the neural correlates of timekeeping functions. Both encoding and memory retrieval components for time perception are impaired in Parkinson's disease (PD). The aim of our study was to investigate in hemi-Parkinsonian patients the existence of a specific alteration in memory for time depending on the affected side, to better understand the contribution of the left or right basal ganglia circuits in different components of time perception. Right and left hemi-PD patients performed a time reproduction task in which they were required to reproduce in the same session short (5 s) and long (15 s) time intervals, in off- and on-therapy condition. Whil…

Brain activity during intra- and cross-modal priming: new empirical data and review of the literature

A positron emission tomography (PET) study was conducted to investigate the neurofunctional correlate of auditory within-modality and auditory-to-visual cross-modality stem completion priming. Compared to the auditory-to-auditory priming condition, cross-modality priming was associated with a significantly larger regional cerebral blood flow (rCBF) decrease at the boundary between left inferior temporal and fusiform gyri, brain regions previously associated with modality independent lexical retrieval and reading. Instead, within-modality auditory priming was associated with a bilateral pattern of prefrontal rCBF increase. This was likely the expression of more efficient access to output lex…

Impaired reproduction of second but not millisecond time intervals in Parkinson's disease

The basal ganglia have been associated with temporal processing in ranges of milliseconds and seconds. However, results from PD patient studies are elusive. Time perception in these patients has been tested with different approaches including repetitive movement tasks (i.e. finger tapping) and cognitive tasks (i.e. time reproduction), and both abnormal and normal performances have been reported for different time intervals. Furthermore, when PD patients were required to learn two target durations in the same session when they were off medication, they overestimated the short duration and underestimated the long duration in the seconds range. This pattern of temporal accuracy was described a…

Fast increase of motor cortical inhibition following postural changes in healthy subjects.

BACKGROUND AND AIMS: Postural reactions are associated with changes in the excitability of the motor system. In the present study we investigated the presence of neurophysiological changes of motor cortical areas targeting muscles of the inferior limbs following treatment with a physiotherapy technique aimed to treat postural dysfunctions by stretching postural muscles, global postural reeducation (GPR). METHODS: Twenty healthy subjects were evaluated with paired-transcranial magnetic stimulation (TMS) of the motor cortex and recording of motor evoked potentials (MEPs) from peripheral muscles of the inferior limb before and after two GPR manoeuvres applied in different experiments (1 and 2)…

Long-term effects on motor cortical excitability induced by repeated muscle vibration during contraction in healthy subjects

article i nfo Objective: The effects of a novel repeated muscle vibration intervention (rMV; 100 Hz, 90 min over 3 consecutive days) on corticomotor excitability were studied in healthy subjects. Methods: rMV was applied over the flexor carpi radialis (FCR) during voluntary contraction (experiment 1), during relaxation and during contraction without vibration (experiment 2). Focal transcranial magnetic stimulation (TMS) was applied before rMV and one hour, and one, two and three weeks after the last muscle vibration intervention. At each of these time points, we assessed the motor map area and volume in the FCR, extensor digitorum communis (EDC) and abductor digiti minimi (ADM). Short-inter…

Movements Execution in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer’s Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunct…

The what and how of observational learning

Abstract Neuroimaging evidence increasingly supports the hypothesis that the same neural structures subserve the execution, imagination, and observation of actions. We used repetitive transcranial magnetic stimulation (rTMS) to investigate the specific roles of cerebellum and dorsolateral prefrontal cortex (DLPFC) in observational learning of a visuomotor task. Subjects observed an actor detecting a hidden sequence in a matrix and then performed the task detecting either the previously observed sequence or a new one. rTMS applied over the cerebellum before the observational training interfered with performance of the new sequence, whereas rTMS applied over the DLPFC interfered with performa…

RELATIVISTIC COMPRESSION AND EXPANSION OF EXPERIENTIAL TIME IN THE LEFT AND RIGHT SPACE

Time, space and numbers are closely linked in the physical world. However, the relativistic-like effects on time perception of spatial and magnitude factors remain poorly investigated. Here we wanted to investigate whether duration judgments of digit visual stimuli are biased depending on the side of space where the stimuli are presented and on the magnitude of the stimulus itself. Different groups of healthy subjects performed duration judgment tasks on various types of visual stimuli. In the first two experiments visual stimuli were constituted by digit pairs (1 and 9), presented in the centre of the screen or in the right and left space. In a third experiment visual stimuli were constitu…

Subthalamic deep brain stimulation improves time perception in Parkinson's disease.

Alterations in temporal estimation have been observed in Parkinson's disease (PD) and have been associated with dopaminergic dysfunction. To investigate whether deep brain stimulation might reverse these abnormalities in PD, patients treated with electrode implantation for subthalamic deep brain stimulation were required to reproduce time intervals in different experimental conditions (off deep brain stimulation/off therapy, on deep brain stimulation/off therapy, on therapy/off deep brain stimulation). Patients treated with deep brain stimulation in off deep brain stimulation/off therapy displayed the anomalous pattern of responses typically observed in PD. When subthalamic deep brain stimu…

Prismatic Adaptation as a Novel Tool to Directionally Modulate Motor Cortex Excitability: Evidence From Paired-pulse TMS

Abstract Background The prismatic adaptation (PA) is a visuo-motor procedure that has captured the attention of neuroscientists in the last decades, hence it seems to affect high-order cognition. However, the basic neural processes related to PA and its effects on cortical plasticity are not clear yet. Objective/hypothesis The aim of the present study is to explore whether PA induces a direct effect on the motor cortices (M1) excitability. Methods Fourteen healthy participants were submitted to paired-pulse TMS to measure short-intracortical-inhibition (SICI) and intracortical-facilitation (ICF) on both the left and the right M1, before and after PA, that could induce a leftward or rightwar…

TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with …

Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans.

Connections between the cerebellum and the contralateral motor cortex are dense and important, but their physiological significance is difficult to measure in humans. We have studied a group of 10 healthy subjects to test whether a modulation of the excitability of the left cerebellum can affect the excitability of the contralateral motor cortex. We used repetitive transcranial magnetic stimulation (rTMS) at 1 Hz frequency to transiently depress the excitability of the left cerebellar cortex and paired-pulse TMS testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) to probe the excitability of cortico-cortical connections in the right motor cortex. The cortical sile…

Motor and linguistic linking of space and time in the cerebellum

Background: Recent literature documented the presence of spatial-temporal interactions in the human brain. The aim of the present study was to verify whether representation of past and future is also mapped onto spatial representations and whether the cerebellum may be a neural substrate for linking space and time in the linguistic domain. We asked whether processing of the tense of a verb is influenced by the space where response takes place and by the semantics of the verb. Principal Findings: Responses to past tense were facilitated in the left space while responses to future tense were facilitated in the right space. Repetitive transcranial magnetic stimulation (rTMS) of the right cereb…

The role of transcranial magnetic stimulation in the study of cerebellar cognitive function.

Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of brain structures. This technique can be used either for stimulating the motor cortex, recording motor evoked potentials from peripheral muscles, or for modulating the excitability of other non-motor areas in order to establish their necessity for a given task. TMS of the cerebellum can give interesting insights on the cerebellar functions. Paired-TMS techniques, delivering stimuli over the cerebellum followed at various interstimulus intervals by stimuli over the motor cortex, allow studying the pattern of connectivity between the cerebellum and the contralateral motor cortex in physiological as well as in pathologic…

Overestimation of numerical distances in the left side of space

Normal subjects presented with a middle number and two left- and right-sided outer numbers overestimate the numerical distance between the middle number and that positioned at its left side. Repetitive transcranial magnetic stimulation (rTMS) of the right posterior parietal cortex specifically counteracts this bias, suggesting that the mental representation of space defined by numbers is shifted toward the left side depending on a greater activity of the right hemisphere.

Remembering what but not where: independence of spatial and visual working memory in the human brain

We report the neuropsychological and MRI investigation of a patient (MV) who developed a selective impairment of visual-spatial working memory (WM) with preservation not only of verbal, but also of visual shape WM, following an ischemic lesion in the cerebral territory supplied by one of the terminal branches of the right anterior cerebral artery. MV was defective in visual-spatial WM whether the experimental procedure involved arm movement for target pointing or not. Also, in agreement with the role generally assigned to visual-spatial WM in visual imagery. MV was extremely slow in the mental rotation of visually and verbally presented objects. In striking contrast with the WM deficit, MV'…

Parkinsonian Patients with Deficits in the Dysexecutive Spectrum are Impaired on Theory of Mind Tasks

Understanding the mental states of others entails a number of cognitive processes known as Theory of Mind (ToM). A relationship between ToM deficits and executive disorders has been hypothesized in individuals with Parkinson's disease (PD). The present study was aimed at investigating the effect of dysexecutive deficits on ToM abilities in PD patients without dementia. Participants included 30 PD patients and 30 healthy subjects (HC). PD patients were divided into two groups according to their executive test performance: patients with poor (dysexecutive group; n = 15) and normal (executively unimpaired group; n = 15) performance. All participants were administered faux pas recognition writt…

Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect

Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse ove…

Interference of left and right cerebellar rTMS with procedural learning.

Abstract Increasing evidence suggests cerebellar involvement in procedural learning. To further analyze its role and to assess whether it has a lateralized influence, in the present study we used a repetitive transcranial magnetic stimulation interference approach in a group of normal subjects performing a serial reaction time task. We studied 36 normal volunteers: 13 subjects underwent repetitive transcranial magnetic stimulation on the left cerebellum and performed the task with the right (6 subjects) or left (7 subjects) hand; 10 subjects underwent repetitive transcranial magnetic stimulation on the right cerebellum and performed the task with the hand ipsilateral (5 subjects) or contral…

Parieto-frontal interactions in visual-object and visual-spatial working memory: Evidence from transcranial magnetic stimulation

This study aimed to investigate whether transcranial magnetic stimulation (TMS) can induce selective working memory (WM) deficits of visual-object versus visual-spatial information in normal humans. Thirty-five healthy subjects performed two computerized visual n-back tasks, in which they were required to memorize spatial locations or abstract patterns. In a first series of experiments, unilateral or bilateral TMS was delivered on posterior parietal and middle temporal regions of both hemispheres after various delays during the WM task. Bilateral temporal TMS increased reaction times (RTs) in the visual-object, whereas bilateral parietal TMS selectively increased RTs in the visual-spatial W…

Apolipoprotein E genotype does not influence the progression of multiple sclerosis

OBJECTIVE: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS. METHODS: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the -491 A/T polymorphism of the APOE promoter were determined. RESULTS: No association was observed between the APOE epsilon4 allele and clinical characteristics of our study population. We also investiga…

High frequency rTMS over the left parietal lobule increases non-word reading accuracy

Increasing evidence in the literature supports the usefulness of Transcranial Magnetic Stimulation (TMS) in studying reading processes. Two brain regions are primarily involved in phonological decoding: the left superior temporal gyrus (STG), which is associated with the auditory representation of spoken words, and the left inferior parietal lobe (IPL), which operates in phonological computation. This study aimed to clarify the specific contribution of IPL and STG to reading aloud and to evaluate the possibility of modulating healthy participants' task performance using high frequency repetitive TMS (hf-rTMS). The main finding is that hf-rTMS over the left IPL improves non-word reading accu…

Intact cross-modality text-specific repetition priming in patients with Alzheimer’s disease

This study was aimed at investigating the basic mechanisms of the normal repetition priming evoked by text re-reading procedures in Alzheimer's disease (AD) patients (Monti, Gabrieli, Wilson, &amp; Reminger, 1994; Monti et al., 1997). For this purpose, we contrasted the reading facilitation elicited by previous reading or listening to a text in a sample of AD patients and a group of age-matched normal controls. Consistent with previous evidence in normal undergraduates (Levy &amp; Kirsner, 1989), previous listening to a text decreased the successive reading time of the same text (cross-modality priming). However, the reading facilitation elicited by previous reading of the same text (within…

An exploration of anger phenomenology in multiple sclerosis

Background and purpose:  Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. Patients and methods:  About 195 cognitively unimpaired MS patients (150 relapsing–remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients’ anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of …